Static and statistical bending of DNA evaluated by Monte Carlo simulations.

Abstract

To investigate the influence of thermal fluctuations on DNA curvature the Metropolis procedure at 300 K was applied to B-DNA decamers containing ACT5 and A4-T4 blocks. Monte Carlo simulations have confirmed the DNA bending anisotropy: B-DNA bends most easily in a groove direction (roll). The AN5TS block is more rigid than the other sequences; the pyrimidine-purine dimers are found to be the most flexible. For AjTCTCT, A5CTCTC, and ASGAGAG, the average Iad angle per decamer is 20-25o in a direction toward the minor grve in the center of the ACTS tract, which is consistent with both the "junction" and "wedge AA" models.However, in AiTs, A4T4CG, and T4A4GC, bending is directed into the grooves at the 5' and 3' ends of purine tracts. Thus, directionality of bending caused by A.T. blocks strongly depends on their neighboring sequences. These calculations demonstrate that the sequence-dependent variation of the minor-groove width mimics the observed hydroxyl radical cleavage pattern. To estimate the effect of fluctuations on the overall shape of curved DNA fragments, longer pieces of DNA (up to 200 base pairs) were generated. For sequences with strong curvature (AsXS and A4T4CG), the static model and Monte Carlo ensemble give similar results but, for moderately and slightly curved sequences (AsT5 or T4A4GC), the static model predicts a much smaller degree of bending than does the statistical representation. Considering fluctuations is important for quantitative interpretation of the gel electrophoresis measurements of DNA curvature, where both the static and statistical bends are operative.The intrinsic bending (or curvature) ofDNA is closely related to numerous biological processes-e.g., packaging in chromatin, gene regulation, and recombination (for reviews, see refs. 1-3). The curved DNA sequences demonstrate anomalously slow migration in polyacrylamide gel electrophoresis experiments. Several models were suggested recently (4-6) to quantitatively describe -this phenomenon. These models neglect thermal fluctuations and deal with some static parameters, "junction" angles (4) or the "wedge" angles (1, 6). Whereas the junction model phenomenologically describes bending of DNA containing A",T, blocks, the two wedge models (5, 6) claim to predict curvature of DNA with an arbitrary sequence at the base step level; however, they differ significantly in the values of the wedge angles. In our view, there are two shortcomings to that approach. (i) The wedge angles are comparable to or smaller than the corresponding fluctuations, estimated as 5-7°based on the persistence length of DNA as 500 A (7). (ii) There is an asymmetry in DNA bending: it bends to different extents into the minor and major grooves (8-10), so the average bend angle can deviate significantly from the energetically optimal one.The problem of averaging is not trivial in this case. Direct use of the averages of the microscopic parameters does not necessarily produce an adequate description of the macroscopic shape of curved DNA. Indeed, parameters def...

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